Post-operative Electrical Muscle Stimulation to Stimulate Muscle Protein Synthesis in Humans

NCT05997095 | Active Not Recruiting

• 1 other identifier: FMHS 261-0423
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Skeletal muscle accounts for approximately 45-55% of total body mass in healthy adults and plays a pivotal role in whole-body metabolic health, locomotion and physical independence. Undesirable loss of skeletal muscle mass (atrophy) is, however, a common feature of many communicable and non-communicable diseases including ageing, bed-rest/immobilisation, cancer and physical inactivity. As such, the design of optimal strategies (e.g., different types of exercise) to "offset" these detrimental losses of muscle is a focus for both researchers and clinicians. One situation where losses of muscle mass occur very quickly (i.e., within a few days) is after surgery. However, at this time, most people (especially if they have had major abdominal or lower-limb surgery) are not able to perform exercise and as such a different strategy to maintain muscle mass needs to be found. It has been shown that electrical stimulation of the leg muscles can maintain muscle mass and function in patients after surgery. It is not however yet known, what the optimal electrical stimulation regime is to preserve muscle mass during situations of disuse. This study aims to examine the impact of three different electrical stimulation protocols on muscle building processes in individuals age-matched to those most commonly presenting for major abdominal surgery. This information will then be used in a clinical trial of surgical patients to see if it can preserve their muscle mass and function in the post-operative period.

Conditions

Skeletal Muscle Atrophy

Keywords

Muscle; Protein Synthesis; Neuromuscular electrical stimulation; Muscle blood flow

Outcome Measures

Primary Outcomes (1)

• Skeletal Muscle Protein Synthesis

  A primed continuous infusion of a stable isotope tracer (1,2 13C2\] leucine) will be initiated (Prime: 0.7 mg/kg; Constant: 1.0 mg/kg/h) at time 0h. After 60 min of stable isotope infusion, a single muscle biopsy will be taken from one leg. Another biopsy from the same leg will be taken 120 min later, and a third 240 min after the second to provide rates of muscle protein synthesis in the rested condition and in response to NMES, respectively. The fractional synthetic rate (FSR) of the myofibrillar fraction was calculated from the incorporation of \[1,2 13C2\] leucine, using venous plasma labelling between muscle biopsies to represent the immediate precursor for protein synthesis. This will give a rate (%/hour) of muscle protein synthesis.

  4 hours

Secondary Outcomes (2)

• Skeletal Muscle Anabolic Signalling

  4 hours

• Skeletal Muscle Blood Flow

  Baseline and 30 minutes post neuromuscular stimulation

Other Outcomes (1)

• Perceived discomfort of Neuromuscular Electrical stimulation

  Immediately post neuromuscular stimulation

Study Arms (3)

30Hz (low-intensity)

ACTIVE COMPARATOR

Volunteers receive 30 mins of neuromuscular electrical stimulation at 30Hz with a contraction pattern of 1 second "on" and 1 second "off"

Other: Neuromuscular electrical stimulation (NMES/0

100Hz (higher-intensity)

EXPERIMENTAL

Volunteers receive 30 mins of neuromuscular electrical stimulation at 100Hz with a contraction pattern of 1 second "on" and 1 second "off"

Other: Neuromuscular electrical stimulation (NMES/0

30Hz (low-intensity, 3:1)

EXPERIMENTAL

Volunteers receive 30 mins of neuromuscular electrical stimulation at 30Hz with a contraction pattern of 3 seconds "on" and 1 second "off"

Other: Neuromuscular electrical stimulation (NMES/0

Interventions

Neuromuscular electrical stimulation (NMES/0 OTHER

NMES will be applied for 30 min and will be delivered using an approved, CE-marked device (Premier Combo Plus, Med-Fit Ltd, UK) using two large (7.5 × 13 cm) electrodes placed proximally and distally over the lateral quadriceps. The set protocols will be pre-programmed into to the device and the amplitude value will match the setting that was determined during a familiarisation visit

100Hz (higher-intensity); 30Hz (low-intensity); 30Hz (low-intensity, 3:1)

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 60-85 y
• Willing and able to give informed consent for participation in the study

You may not qualify if:

• BMI \<18.5 or \>35kg/m2
• Participation in any regular, structured RET within the past 6 months
• Musculoskeletal disorders
• Severe respiratory disease:
• COPD
• Pulmonary hypertension
• Neurological disorders:
• Cerebrovascular disease (cerebral haemorrhage; cerebral ischemic stroke)
• Intracranial space-occupying lesion
• Epilepsy
• Metabolic disease:
• Hyper and hypo parathyroidism
• Untreated hyper and hypothyroidism
• Cushing's disease
• Type 1 or 2 diabetes

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

University of Nottingham

Nottingham, Nottinghamshire, NG7 2RD, United Kingdom

Location

Related Publications (5)

• Hardy EJ, Hatt J, Doleman B, Smart TF, Piasecki M, Lund JN, Phillips BE. Post-operative electrical muscle stimulation attenuates loss of muscle mass and function following major abdominal surgery in older adults: a split body randomised control trial. Age Ageing. 2022 Oct 6;51(10):afac234. doi: 10.1093/ageing/afac234.

  PMID: 36315433 BACKGROUND

• Hardy EJO, Inns TB, Hatt J, Doleman B, Bass JJ, Atherton PJ, Lund JN, Phillips BE. The time course of disuse muscle atrophy of the lower limb in health and disease. J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2616-2629. doi: 10.1002/jcsm.13067. Epub 2022 Sep 14.

  PMID: 36104842 BACKGROUND

• Wall BT, Dirks ML, Verdijk LB, Snijders T, Hansen D, Vranckx P, Burd NA, Dendale P, van Loon LJ. Neuromuscular electrical stimulation increases muscle protein synthesis in elderly type 2 diabetic men. Am J Physiol Endocrinol Metab. 2012 Sep 1;303(5):E614-23. doi: 10.1152/ajpendo.00138.2012. Epub 2012 Jun 26.

  PMID: 22739107 BACKGROUND

• Mancinelli R, Toniolo L, Di Filippo ES, Doria C, Marrone M, Maroni CR, Verratti V, Bondi D, Maccatrozzo L, Pietrangelo T, Fulle S. Neuromuscular Electrical Stimulation Induces Skeletal Muscle Fiber Remodeling and Specific Gene Expression Profile in Healthy Elderly. Front Physiol. 2019 Nov 27;10:1459. doi: 10.3389/fphys.2019.01459. eCollection 2019.

  PMID: 31827446 BACKGROUND

• Burd NA, Andrews RJ, West DW, Little JP, Cochran AJ, Hector AJ, Cashaback JG, Gibala MJ, Potvin JR, Baker SK, Phillips SM. Muscle time under tension during resistance exercise stimulates differential muscle protein sub-fractional synthetic responses in men. J Physiol. 2012 Jan 15;590(2):351-62. doi: 10.1113/jphysiol.2011.221200. Epub 2011 Nov 21.

  PMID: 22106173 BACKGROUND

MeSH Terms

Conditions

Muscular Atrophy

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Translational Physiology

Study Record Dates

• First Submitted: August 10, 2023
• First Posted: August 18, 2023
• Study Start: May 22, 2023
• Primary Completion: September 28, 2025
• Study Completion: December 28, 2025
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)